C&I ACS News: Liver Mimic Spares Animals

Liver mimic spares animalsCath O’Driscoll - April 2014

A ‘chemosynthetic liver’ that metabolises drugs and other substances just like the real one could dramatically speed the development of new drugs, and lower costs, by slashing numbers of animal experiments. It promises to be especially helpful in studying the side effects of multiple drug-drug and drug-food interactions, ￼￼￼￼according to researchers describing the technology at the ACS meeting in Dallas, Texas, in March 2014 – and can even detect some metabolites that animal tests miss. ‘Some animals are always going to be needed in the development of pharma products, but if we can minimise animal testing, that is a good thing,’ said Mukund Chorghade, chief scientific officer at Empiriko Corporation in Newton, Massachusetts, US, which holds the patent on the Biomimiks liver technology. ‘We are seeing extraordinary results, making metabolites including epoxides and hydrates normally missed with traditional animal tests.’

The human liver contains large numbers of cytochrome P450 enzymes that break down drugs and other substances into a range of metabolites, some of which may elicit harmful side effects. Instead, the chemosynthetic liver comprises a cocktail of just 20 or 30 synthetic catalysts – azamacrocycles including porphyrins as in blood – that essentially do the same job, Chorghade explained. So now, rather than using lab animals, researchers can work out the metabolic profiles of drugs simply by mixing them with the new Biomimiks livers in test tubes.

While the technology is now available for research purposes, it is not yet approved as a substitute for animal tests. However, researchers have already tested 52 drugs using Biomimiks, and Chorghade says the results correlate ‘extremely well in all cases’ with those from animal experiments. In tests of two drugs commonly taken together, one for high cholesterol and the other for Type 2 diabetes, they found that the cholesterol drug sped up the breakdown of the other drug, which could potentially lower its effectiveness.

To obtain US Food and Drug Administration (FDA) approval, Chorghade says they would need to test Biomimiks on 100 drugs.